Oxalyl chloride → N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamide

HRID 925964노트

반응식

HRID 925964 반응식
[CH:1]([C:4]1[O:8][N:7]=[C:6]([C:9]([OH:11])=O)[CH:5]=1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[C:24]([Cl:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][C:20]=1[C:28](=[O:30])[CH3:29].C([O-])(O)=O.[Na+]>C(Cl)Cl.O1CCOCC1.CN(C=O)C>[C:28]([C:20]1[C:19]([NH:18][C:9]([C:6]2[CH:5]=[C:4]([CH:1]([CH3:2])[CH3:3])[O:8][N:7]=2)=[O:11])=[C:24]([Cl:25])[C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)(=[O:30])[CH3:29]

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 64838125-(Propan-2-yl)-1,2-oxazole-3-carboxylic acidHCID 299199881-(2-Amino-3-chloro-4-methoxyphenyl)ethanone

생성물 1

HCID 66650637N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamide수율 60%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

실험 절차

To a stirred solution of 5-isopropylisoxazole-3-carboxylic acid (3.5 g, 22.6 mmol) in DCM (35 mL) was added anhydrous DMF (few drops) and oxalyl chloride (3.82 mL, 43.2 mmol) at 0° C. under nitrogen. At the end of the gas escape, the reaction mixture was allowed to warm up to room temperature. The mixture was stirred at room temperature for 2 hrs and was evaporated. Dioxane (70 mL) was added under nitrogen, followed by a solution of 1-(2-amino-3-chloro-4-methoxy-phenyl)-ethanone 201d (4.10 g, 20.6 mmol) in dioxane (15 mL). The reaction mixture was stirred at room temperature for 16 hrs. NaHCO3 was then added. The mixture was extracted with EtOAc. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was triturated in Et2O to yield compound 241d as a brown solid in 60% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.47 (s, 3H), 1.48 (s, 3H), 1.76 (brs, 1H), 2.57 (s, 3H), 3.34-3.40 (m, 1H), 3.98 (s, 3H), 6.86 (d, J=8.53 Hz, 1H), 7.64 (d, J=8.53 Hz, 1H), 8.07 (s, 1H).

후처리

  1. customwas evaporated
  2. additionDioxane (70 mL) was added under nitrogen
  3. stirringThe reaction mixture was stirred at room temperature for 16 hrs
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialOrganics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was triturated in Et2O

출처 및 근거

ORD 기록
ord-89d06834949a44b3a579d0482561ff54
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284307B2

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